crossing96/oncoscreening huggingface dataset:
Urothelial cancer organoids: a tool for bladder cancer research.	"BACKGROUND: Bladder cancer ranks among the top ten most common tumor types worldwide and represents a growing healthcare problem, accounting for a large part of total healthcare costs. Chemotherapy is effective in a subset of patients, while causing severe side effects. Tumor pathogenesis and drug resistance mechanisms are largely unknown. Precision medicine is failing in bladder cancer, as bladder tumors are genetically and molecularly very heterogeneous. Currently, therapeutic decision-making depends on assessing a single fragment of surgically acquired tumor tissue. OBJECTIVE: New preclinical model systems for bladder cancer are indispensable for developing therapeutic strategies tailored to individual patient and tumor characteristics. Organoids are small 3D tissue cultures that simulate small-size organs ""in a dish"" and tumoroids are a special type of cancer organoid (i.e., malignant tissue). MATERIALS AND METHODS: Since 2016, we have collaborated with the renowned Hubrecht Institute to provide proof of concept of tissue-based bladder tumoroids mimicking parental tumors. We have developed a living biobank containing bladder organoids and tumoroids grown from over 50 patient samples, which reflect crucial aspects of bladder cancer pathogenesis. RESULTS: Histological and immunofluorescence analysis indicated that the heterogeneity and subclassification of tumoroids mimicked those of corresponding parental tumor samples. Thus, urothelial tumoroids mimic crucial aspects of bladder cancer pathogenesis. CONCLUSION: Research with urothelial tumoroids will open up new avenues for bladder cancer pathogenesis and drug-resistance research as well as for precision medicine approaches."	bladder
The emerging treatment landscape of advanced urothelial carcinoma.	PURPOSE OF REVIEW: Urothelial carcinoma (UC) is one of the most common malignancies in the Western world. Historically, patients with advanced disease have had a poor prognosis and progress within months of completing upfront platinum-based chemotherapy. In the last two years, the treatment landscape for metastatic UC (mUC) has significantly shifted with the emergence of contemporary immunotherapy and targeted agents. The purpose of this review is to highlight the current and emerging systemic treatment options for mUC of the bladder. RECENT FINDINGS: PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have demonstrated activity in the postplatinum and platinum-ineligible settings. Additionally, they have become a standard maintenance treatment option after avelumab demonstrated increased overall survival in patients with stable disease or better after first line platinum-based chemotherapy. Novel targeted therapies and antibody-drug conjugates (ADCs) have been granted Food and Drug Administration approval for subsequent line therapy based on promising results in phase II and III trials. SUMMARY: There has been a considerable increase in the variety of effective therapies for mUC, including the utility of ICIs, novel targeted agents, and ADCs. Platinum-based chemotherapy remains an effective first-line option. As the role of novel therapies continues to shift toward earlier in the disease course, there remains an important need to develop feasible, globally accessible predictive biomarkers that can aid in patient selection and inform sequencing of therapeutic options.	bladder
Radical Cystectomy vs. Radiotherapy in Urothelial Bladder Cancer in Elderly and Very Elderly Patients.	INTRODUCTION: Controversy regarding cancer-specific mortality (CSM) of elderly and very elderly patients with muscle-invasive, non-metastatic, urothelial carcinoma of the urinary bladder (UCUB) undergoing radical cystectomy (RC) vs radiotherapy (RT) still exists. MATERIALS AND METHODS: In the 2004-2016 Surveillance, Epidemiology and End Results (SEER) database, we identified 2663 UCUB patients aged 75-79 (1808 RC vs 855 RT) and 3569 UCUB patients aged 80-89 (1551 RC vs 2018 RT). After stratification for concomitant chemotherapy, propensity score matching (PSM) between RC and RT was applied and competing-risks regression models addressed CSM and OCM. RESULTS: In the cohort aged 75-79, five-year CSM rates were 22.0 vs 49.0% for RC only vs RT only and yielded a HR of 0.41 (95% confidence interval (CI) 0.30-0.57, p<0.001) favoring RC only. Five-year CSM rates were 28.3 vs 44.3% for RC with chemotherapy vs trimodal therapy (TMT) and yielded a HR of 0.48 (95% CI 0.35-0.65, p<0.001) favoring RC with chemotherapy. In the cohort aged 80-89, five-year CSM rates were 24.2 vs 48.9% for RC only vs RT only and yielded a HR of 0.42 (95% CI 0.33-0.52, p<0.001) favoring RC only. Five-year CSM rates were 19.6 vs 43.2% for RC with chemotherapy vs TMT and yielded a HR of 0.43 (95% CI 0.28-0.67, p<0.001) favoring RC with chemotherapy. CONCLUSIONS: In elderly and very elderly patients, radical cystectomy is associated with virtually half the CSM rate than radiotherapy, regardless of concomitant chemotherapy administration.	bladder
Role of hypermethylated-lncRNAs in the prognosis of bladder cancer patients.	OBJECTIVE: To explore the hypermethylated long non-coding (lnc)RNAs involved in bladder carcinogenesis and prognosis. METHODS: Reduced representation bisulfite sequencing and RNA sequencing were performed on five paired tumor and adjacent normal tissue samples from bladder cancer patients. The differentially methylated regions around transcription start sites and differentially expressed genes, including lncRNAs, were analyzed. Correlations between DNA methylation modifications and the expression of lncRNAs were examined. Survival analysis was surveyed on the GEPIA web server. RESULTS: We identified 19,560 hypomethylated and 68,781 hypermethylated differentially methylated regions around transcription start sites in bladder cancer tissues. In total, 2321 differentially expressed genes were found in bladder tumors, among which, 367 were upregulated and 1954 were downregulated. There were 141 downregulated genes involving eight lncRNAs that were consistently hypermethylated, while 24 upregulated genes were consistently hypomethylated. Survival analysis demonstrated that hypermethylation of lncRNAs LINC00683 and MSC-AS1 were associated with poor overall survival in bladder cancer patients. CONCLUSION: Some lncRNAs are controlled by DNA methylation in bladder cancer and they might be important factors in bladder carcinogenesis. Hypermethylated lncRNAs including LINC00683 and MSC-AS1 have the potential to be prognostic biomarkers for bladder cancer.	bladder
Multilayer spectrum of intratumoral heterogeneity in basal bladder cancer.	Basal/squamous (Ba/Sq) subtype represents an intrinsic and robust group in the consensus molecular classification of muscle-invasive bladder cancer (MIBC), with poor outcome and controversial chemosensitivity. We aimed to investigate the spectrum of intratumor heterogeneity (ITH) in the Ba/Sq subtype. First, we validated a 29-gene NanoString CodeSet to predict the Ba/Sq subtype for FFPE samples. We identified heterogeneous Ba/Sq tumors in a series of 331 MIBC FFPE samples using dual GATA3/KRT5/6 immunohistochemistry (IHC). Heterogeneous regions with distinct immunostaining patterns were studied separately for gene expression using the 29-gene CodeSet, for mutations by targeted next-generation sequencing, and for copy number alteration (CNA) by microarray hybridization. Among 83 Ba/Sq tumors identified by GATA3/KRT5/6 dual staining, 19 tumors showed heterogeneity at the IHC level. In one third of the 19 cases, regions from the same tumor were classified in different distinct molecular subtypes. The mutational and CNA profiles confirmed the same clonal origin for IHC heterogeneous regions with possible subclonal evolution. Overall, two patterns of intratumoral heterogeneity (ITH) were observed in Ba/Sq tumors: low ITH (regions with distinct immunostaining, but common molecular subtype and shared CNA) or high ITH (regions with distinct immunostaining, molecular subtype, and CNA). These results showed multilayer heterogeneity in Ba/Sq MIBC. In view of personalized medicine, this heterogeneity adds complexity and should be taken into account for sampling procedures used for diagnosis and treatment choice. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.	bladder
Lynch syndrome in urological practice: diagnosis, therapeutic strategies, and screening for upper tract urothelial carcinoma.	PURPOSE OF REVIEW: To provide a comprehensive overview of diagnosis, treatment, and screening for upper tract urothelial carcinoma (UTUC) among Lynch syndrome patients. RECENT FINDINGS: Lynch syndrome is an autosomal dominant disorder resulting from the germline mutation in the mismatch repair (MMR) system. The Lynch syndrome predisposes to early onset of a broad spectrum of tumours, among which UTUC represents the third most frequent malignancy. Since up to 10% of UTUC can be attributed to Lynch syndrome, a correct recognition of this disease provides the opportunity for patients and their relatives to be properly treated for UTUC and to be followed up for other Lynch syndrome-related malignancies. SUMMARY: UTUC patients less than 65 years, or UTUC patients with personal history of Lynch syndrome-related cancer, or with one first-degree relative (FDR) less than 50 years with Lynch syndrome-related cancer, or two FDRs with Lynch syndrome-related cancer regardless of age should be referred to molecular testing and subsequent DNA sequencing to confirm Lynch syndrome diagnosis. Considering the increased risk of metachronous recurrence, treatments other than radical nephroureterectomy, such as ureteroscopic laser ablation may represent valuable therapeutic strategies. As Lynch syndrome patients exhibit an approximate 14-fold increased risk of developing UTUC compared with general population, expert recommendations are urgently required in order to point out appropriate screening protocols.	bladder
Morphological and mechanical changes induced by quercetin in human T24 bladder cancer cells.	Quercetin is a flavonoid found in a great variety of foods such as vegetables and fruits. This compound has been shown to inhibit the proliferation of various types of cancer cells, as well as the growth of tumors in animal models. In the present study, we analyze morphological and mechanical changes produced by quercetin in T24 bladder cancer cells. Decreased cell viability and cell number were observed following quercetin treatment at 40 μM and 60 μM, respectively, as observed by the MTT assay and trypan blue exclusion test, supporting the hypothesis of quercetin anticancer effect. These assays also allowed us to determine the 40, 60, and 80 μM quercetin concentrations for the following analyses, Lactate Dehydrogenase assay (LDH); Nuclear Morphometric Analysis (NMA); and atomic force microscopy (AFM). The LDH assay showed no cytotoxic effect of quercetin on T24 cancer cells. The AFM showed morphological changes following quercetin treatment, namely decreased cell body, cytoplasmic retraction, and membrane condensation. Following quercetin treatment, the NMA evidenced an increased percentage of nuclei characteristic to the apoptotic and senescence processes. Cells also presented biophysical alterations consistent with cell death by apoptosis, as increased roughness and aggregation of membrane proteins, in a dose-dependent manner. Cellular elasticity, obtained through force curves, showed increased stiffness after quercetin treatment. Data presented herein demonstrate, for the first time, in a quantitative and qualitative form, the morphological and mechanical alterations induced by quercetin on bladder cancer cells.	bladder
Robotic-assisted radical cystectomy is associated with lower perioperative mortality in octogenarians.	OBJECTIVES: To compare perioperative outcomes between robotic and open radical cystectomy in octogenarians using real-world data SUBJECTS AND METHODS: Using the Premier Healthcare Database, we found 13,127 patients who underwent robotic-assisted radical cystectomy (RARC) between 2008 and 2017, of which 15.1% were ≥80 years old. Perioperative mortality was the primary outcome of interest. Secondary outcomes include complications, hospital length of stay, readmission rates, and disposition after discharge. Multivariable regression analysis was used to adjust for patient and hospital characteristics. RESULTS: In octogenarians, mortality at the index admission was 2.2% in those who underwent RARC, compared to 4.6% in those who underwent open surgery (P = 0.027). On multivariable analysis, robotic surgery was associated with lower in-hospital mortality in octogenarians (OR 0.46, 95% CI 0.22-0.99, P = 0.047) even after controlling for patient, and hospital characteristics. CONCLUSION: RARC is safe and feasible in octogenarians. Elderly patients may derive more benefit from minimally invasive radical cystectomy compared to a younger cohort.	bladder
Poor clinical outcomes and immunoevasive contexture in SIRPα(+) tumor-associated macrophages enriched muscle-invasive bladder cancer patients.	"OBJECTIVES: In tumor immune microenvironment, the functions of tumor-associated macrophages (TAMs), including phagocytosis and immunomodulatory, have attracted increasing attention recently. With the discovery of CD47-signal regulatory protein-α (SIRPα) as ""don't eat me"" signaling pathway, the role of novel subpopulation of TAMs expressing SIRPα has not been fully elucidated in a wide spectrum of solid tumors including bladder cancer. In this study, we investigated the prognostic and predictive implication of SIRPα(+) TAMs regarding clinical outcomes and adjuvant chemotherapeutic benefit in muscle-invasive bladder cancer (MIBC), and preliminarily characterized the phenotypic features of SIRPα(+) TAMs and its relationship with immune contexture. MATERIALS AND METHODS: A total of 141 histochemical MIBC samples from Zhongshan Hospital (ZS), 45 fresh tissue samples, and 391 MIBC patients from TCGA database were enrolled in this study. SIRPα(+) TAMs was evaluated by immunohistochemical staining of CD68 and SIRPα, and flow cytometry fluorescence staining. RESULTS: Our results illustrated that SIRPα(+) TAMs were enriched in MIBC specimens. Patients with high SIRPα(+) TAMs infiltration suffered significant poor overall survival and recurrence-free survival (P = 0.0030 and P = 0.0282). SIRPα(+) TAMs infiltration was an independent prognosticator in multivariate Cox model. Moreover, adjuvant chemotherapy (ACT) application showed significantly survival benefit in patients with low SIRPα(+) TAMs infiltration (P = 0.0135). SIRPα(+) TAMs with suppressive phenotype exhibited a positive correlation with immune tolerance and dysfunctional CD8(+) T cells in MIBC. CONCLUSIONS: SIRPα(+) TAMs infiltration indicated poor prognosis and ACT resistance in MIBC. Immunosuppressive SIRPα(+) TAMs is closely related to immune evasion with exhausted T cells states, suggesting the prospect of SIRPα(+) TAMs as a potential therapeutic target in MIBC."	bladder
Characterization of receptor tyrosine kinase activation and biological activity of toceranib phosphate in canine urothelial carcinoma cell lines.	BACKGROUND: Urothelial carcinoma (UC) accounts for > 90% of canine tumors occurring in the urinary bladder. Toceranib phosphate (TOC) is a multi-target receptor tyrosine kinase (RTK) inhibitor that exhibits activity against members of the split kinase family of RTKs. The purpose of this study was to evaluate primary UC tumors and UC cell lines for the expression and activation of VEGFR2, PDGFRα, PDGFRβ, and KIT to assess whether dysregulation of these RTKs may contribute to the observed biological activity of TOC. RESULTS: Transcript for VEGFR2, PDGFRα, PDGFRβ, and KIT was detected in all UC tissue samples and UC cell lines. The Proteome Profiler™ Human Phospho-RTK Array Kit (R & D Systems) provided a platform to assess phosphorylation of 42 different RTKs in primary UC tumors and UC cell lines. Evidence of PDGFRα and PDGFRβ phosphorylation was present in only 11% or 33% of UC tumors, respectively, and 25% of UC cell lines. Treatment of UC cell lines with TOC had no significant impact on cell proliferation, including UC cell lines with evidence of PDGFRβ phosphorylation. CONCLUSIONS: Phosphorylation of several key RTKs targeted by TOC is present in a small subset of primary UC tumors and UC cell lines, suggesting that these RTKs do not exist in a state of continuous activation. These data suggest that activation of RTKs targeted by TOC is present in a small subset of UC tumors and UC cell lines and that treatment with TOC at physiologically relevant concentrations has no direct anti-proliferative effect on UC cells.	bladder
Perioperative outcomes of intracorporeal robot-assisted radical cystectomy versus open radical cystectomy: A systematic review and meta-analysis of comparative studies.	PURPOSE: To systematically review studies comparing the perioperative outcomes of intracorporeal robot-assisted radical cystectomy (iRARC) and open radical cystectomy (ORC). METHODS: Systematic searches of PubMed, Web of Science and the Cochrane Library were performed in June 2020. Studies with data comparing iRARC and ORC were included in our review, and a pooled meta-analysis was completed. RESULTS: In total, 8 studies (7 prospective studies, 1 retrospective study) comparing 1193 patients were included for our review and meta-analysis. Compared with ORC, iRARC demonstrated lower estimated blood loss (weighted mean difference (WMD): -449.25; 95% CI -566.47 - -332.03; p < 0.01), lower blood transfusion rates (OR: 0.31; 95% CI 0.22 - 0.46; p < 0.01), and lower postoperative complication rates with Clavien-Dindo grades III-IV (30 days: OR: 0.65; 95% CI 0.47 - 0.90; p = 0.01; 90 days: OR: 0.72; 95% CI 0.53 - 0.98; p = 0.04), but a longer operative time (WMD: 78.82; 95% CI 52.77 - 104.87; P < 0.01). Furthermore, there was no significant difference between iRARC and ORC in terms of postoperative complication rates with Clavien-Dindo grades Ⅰ-Ⅱ (30 days: OR: 0.71; 95% CI 0.36 - 1.40; p = 0.32; 90 days: OR: 0.98; 95% CI 0.74 - 1.30; p = 0.89), length of stay (WMD: -1.18; 95% CI -3.33 - -2.07; p = 0.06) and positive surgical margins (OR: 0.78; 95% CI 0.0.45 - 1.36; p = 0.38). CONCLUSION: iRARC was associated with a significantly lower estimated blood loss and a lower blood transfusion rate and major postoperative complication rate than ORC.	bladder
Downregulating testosterone levels enhance immunotherapy efficiency.	Low response rates to certain tumor types remain a major challenge for immune checkpoint blockade therapy. In this study, we first conducted an integrated biomarker evaluation of bladder cancer patients from confirmatory cohorts (IMvigor210) and found that no significant differences exist between sexes before acceptance of anti-PD-L1 treatment, whereas male patients showed a better response. Thus, we then focused on sex-related changes post anti-PD-L1 treatment and found no obvious impact on the gut microbiota in male mice but a significant decrease in the sex hormone levels. Further, castration dramatically enhanced the antitumor efficacy against murine colon adenocarcinoma in male mice. Moreover, a narrow-spectrum antibiotic, colistin was innovatively used for deregulation of testosterone levels to enhance the immunotherapy efficiency in male mice. These findings indicate that the impact on the sex hormone levels in males may contribute to the sexual dimorphism in response and provide a promising way to enhance immunotherapy efficiency.	bladder
Recombinant BCGs for tuberculosis and bladder cancer.	Bacillus Calmette-Guérin (BCG) vaccine is an attenuated live strain of Mycobacterium bovis. It may be the most widely used vaccine in human history and is the only licensed human tuberculosis (TB) vaccine available. Despite its excellent safety history, a century of use in global vaccination programs, and its significant contribution to reducing TB mortality among children, the efficacy of BCG continues to be disputed due to its incomplete protection against pulmonary TB in adults. Still vaccines offer the best chance to contain the ongoing spread of multi-drug resistance TB and disease dissemination. The development of improved vaccines against TB therefore remains a high global priority. Interestingly, recent studies indicate that genetically modified BCG, or administration of existing BCG through alternate routes, or revaccination, offers improved protection, suggesting that BCG is well poised to make a comeback. Intravesical BCG is also the only approved microbial immunotherapy for any form of cancer, and is the first-line therapy for treatment-naïve non-muscle invasive bladder cancer (NMBIC), which represents a majority of the new bladder cancer cases diagnosed. However, almost a third of patients with NMIBC are either BCG unresponsive or have tumor recurrence, leading to a higher risk of disease progression. With very few advances in intravesical therapy over the past two decades for early-stage disease, and a limited pipeline of therapeutics in Phase 3 or late Phase 2 development, there is a major unmet need for improved intravesical therapies for NMIBC. Indeed, genetically modified candidate BCG vaccines engineered to express molecules that confer stronger protection against pulmonary TB or induce potent anti-tumor immunity in NMIBC have shown promise in both pre-clinical and clinical settings. This review discusses the development of second generation, genetically modified BCG candidates as TB vaccines and as anti-tumor adjuvant therapy for NMIBC.	bladder
Control computerized tomography in neoadjuvant chemotherapy for muscle invasive urinary bladder cancer has no value for treatment decisions and low correlation with nodal status.	BACKGROUND: Control computerized tomography (cCT) is routinely used in many cystectomy centres before the final treatment cycle in patients with muscle-invasive urinary bladder cancer (MIBC) undergoing neoadjuvant chemotherapy (NAC). This is for evaluating response or nonresponse to NAC treatment. In a real-world retrospective cohort, we intended to evaluate the frequency of changed individual treatment strategies following cCT and to investigate any discrepancies between cCT-results on nodal staging and final pN-stages. METHODS: We performed a retrospective data-based, multicenter study of 242 MIBC-patients, staged cT2N0M0-cT4aN0M0, having undergone NAC and radical cystectomy (RC) between 2008 and 2019 at four Swedish cystectomy centres. Statistical analysis was performed using IBM SPSS statistics 26. RESULTS: Overall, 139/242 patients were examined with cCT. Six patients were staged as progressive at cCT and 5/139 (3.6%) underwent a change of previously planned treatment strategy. 2/6 patients with suspected progression (33%) did not change strategy and underwent all preplanned NAC-cycles plus RC. Only 1/6 patients assigned as progressive at the cCT, showed progression in the postoperative pathology specimen. In total 133/139 patients were considered being without progress on cCT, yet 28/133 (21%) presented with nodal progression at postoperative pathology examinations. Only 1/29 patients with histopathologically verified nodal dissemination were detected with cCT, thus 28/29 (96.6%) with pN + were undetected. The sensitivity for cCT to predict pTNM was 17% CI [0%-64%] and the specificity was 78% CI [71%-86%]. CONCLUSIONS: CCT prior to the final treatment cycle of NAC in MIBC, leads to a low percentage of treatment strategy changes and cCT cannot accurately predict pN-status.	bladder